Koumine exhibits anxiolytic properties without inducing adverse neurological effects on functional observation battery, open-field and Vogel conflict tests in rodents

Abstract

Koumine, an active alkaloid of neurotoxic plant Gelsemium, has been focused on its therapeutic uses, especially in central nervous system. Nevertheless, less is known about the neurological effects of koumine, which hampers its potential therapeutic exploitation. Moreover, as the anxiolytic potential of Gelsemium has raised many critical issues, its active principles on the anxiolytic and other neurological effects need to be further investigated. Here, we used functional observation battery (FOB) of mice to systematically measure the neurological effects of koumine at the effective doses, and then further confirmed its anxiolytic properties in open-field test (OFT) of mice and Vogel conflict test (VCT) of rats. Koumine exhibited anxiolytic-like activities but did not affect other autonomic, neurological and physical functions in FOB. Furthermore, koumine released anxiolytic responses and anti-punishment action in a manner similar to diazepam in OFT and VCT, respectively. The results constitutes solid set of fundamental data further demonstrating anxiolytic properties of koumine at the therapeutic doses without inducing adverse neurological effects, which supports the perspectives for the development of safe and effective koumine medicine against pathological anxiety.

Neuropharmacology of Secondary Metabolites from Plants with Anxiolytic and Antidepressant Properties

“…Gelsemine in low doses (10 À6 M and 10 À14 M) administered to male rats for 7 days also showed anxiolytic effects in EPM [73]. Koumine has shown this effect on VCT in mice at doses of 0.167, 0.5, or 1.5 mg/kg [74]. Other reports indicate that the decoction of the African peach root (Nauclea latifolia) injected intraperitoneally in mice produces dose-dependent anxiolytic-like effects (16,40,80, and 160 mg/kg) in EPM.…”

Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

“…First, we found that PK11195 treatment (a TSPO antagonist) is effective for inhibiting the analgesic effect of koumine in CCI-induced NP rats, and that koumine likely contributes to NP by acting on the TSPO. Second, our previous data indicated that koumine increased the levels of allopregnanolone in the spinal cord of CCI rats, thus suggesting that the anti-NP activity of koumine is mediated by the upregulation of allopregnanolone to an adequate level against NP [ 17 ]. Third, an increasing amount of evidence suggests that TSPO and its ligands may be involved in an adaptive response mechanism during neuroinflammation [ 51 , 52 ].…”

“…In previous studies, we found that koumine plays a significant role in the anti-inflammatory and analgesic effects in inflammatory and NP models [ 18 – 21 ]. Interestingly, both the anxiolytic and analgesic effects of koumine may involve the modulation of neurosteroids in the spinal cord [ 17 – 19 ].…”

Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats

“…Koumine, an indole alkaloid isolated from Gelsemium elegans , has shown diverse pharmacological actions including antitumor, anti-inflammatory, anxiolytic, and analgesic activity (Jin et al, 2014; Zhang et al, 2015; Chen et al, 2017). We recently reported the analgesic effect of koumine in various animal pain models, such as chronic constriction injury (CCI), spared nerve injury, diabetic NP, and rheumatoid arthritis pain models (Xu et al, 2012; Ling et al, 2014; Qiu et al, 2015; Yang et al, 2016; Xiong et al, 2017; Jin et al, 2018a).…”